title: N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with dopamine D₂ and 5-Hydroxytryptamine 5HT(1A) activity: synthesis, testing, and molecular modeling.
abstract: The ratio of affinities toward the dopamine D₂ and the 5-hydroxytryptamine 5-HT(1A) receptors is one of the important parameters that determine the efficiency of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para-N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure-activity relationship studies on dopamine D₂ and 5-hydroxytryptamine 5-HT(1A) receptors. It was shown that the biological activity of the described ligands strongly depends on their topology as well as on the nature of the heteroaryl group in the head of the molecules. Docking simulations together with conformational analysis revealed a rational explanation for the ligands' behavior. The molecular model of receptor-ligand interactions described herein provided us with a tool for the rational design of new compounds with a favorable D₂/5-HT(1A) profile.
authors.affiliation: ICTM - Department of Chemistry, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sukalovic
authors.forename: Anca Elena
authors.initials: AE
authors.lastname: Bogdan
authors.forename: Gordana
authors.initials: G
authors.lastname: Tovilovic
authors.forename: Djurdjica
authors.initials: D
authors.lastname: Ignjatovic
authors.forename: Deana
authors.initials: D
authors.lastname: Andric
authors.forename: Sladjana
authors.initials: S
authors.lastname: Kostic-Rajacic
authors.forename: Vukic
authors.initials: V
authors.lastname: Soskic
mesh_terms: D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D008024:Ligands; D017448:Receptors, Dopamine D2; D044282:Receptor, Serotonin, 5-HT1A
keywords: Arylpiperazine; Dopamine receptors; Serotonin receptors